Many biotechnology laboratories and health care institutions use micro- and ultrafiltration methods for processing biological solutions. Examples include the use of such filtration to remove bacteria, to remove suspended solids and contaminants, to concentrate proteins and other macromolecules and to eliminate unwanted micromolecules such as salts.
Centrifugal forces, gas or liquid pressure or vacuum are typically used as the driving force to push or pull solvent and small micromolecules through the membrane while solute components larger than the molecular weight cut-off of the membrane are retained on the feed side of the membrane as retentate or concentrate. In most applications, the higher the pressure or vacuum exerted, the higher is the rate of filtration relative to the membrane surface area used. In general, high speed and small surface area membranes are preferred.
Typical such devices include a chamber for the sample to be processed and a chamber for the capture of the permeate/filtrate, the two chambers being in fluid communication through at least one common aperture across which a membrane such as a microporous ultrafiltration or reverse osmosis membrane is arranged. The membrane is typically sealed fluid-tight at its periphery to the surface at the periphery of the aperture of either the processing/concentration chamber or the permeate chamber, or to both.
The membrane is usually reinforced on its permeate side to withstand transmembrane pressure. There is a feed inlet provided for introducing a liquid sample to the concentration chamber and an outlet for the filtrate from the filtrate chamber. In so-called tangential flow devices there is an additional outlet provided in the concentration chamber to permit recirculation of the liquid sample.
The sealing of the membrane to the filtration device must meet very high requirements so that the liquid to be processed is prevented from by-passing the membrane. The membrane may be sealed in a variety of ways such as by heat-sealing, adhesive- or solvent-bonding, ultrasonic welding or by an interference fit. In addition, material and wall thickness for the chambers which are also sealed together are chosen in order to withstand the operating pressure. Such devices are sometimes also provided with separate pressure holders or membrane assemblies placed between external pressure plates, which are typically bolted together to provide additional support.
One of the problems with such prior art devices is the difficulty in obtaining a satisfactory compromise between, on the one hand, seal reliability for both the membrane and/or for the joint between the chambers to provide adequate pressure containment and, on the other hand, low manufacturing cost.
For practicality and cost reasons, it is desirable to mold such filtration devices but it is not always possible to mold membrane support sections of sufficient thickness to withstand high operating pressures because it is difficult to mix thick and thin areas when molding. The alternative of using separate pressure holders or external pressure plates is both expensive and inconvenient for small devices. Also, although sealing systems that perform well at low to moderate pressures are frequently unreliable at higher pressures.
Another problem is achieving a sufficiently strong seal between the chambers, particularly with incompatible or non-sealing materials and in large surface area devices that must withstand higher overall pressures.
The design of one such centrifugal filtration device is described in U.S. Pat. No. 5,647,990, which discloses a half cylindrical sleeve to retain the filtration membrane in place over the aperture between the concentration and filtrate chambers. A principal drawback of that design is its potential for damaging the relatively fragile membrane when the retaining sleeve is pushed over the concentration chamber, since the resultant frictional forces tend to push the membrane out of alignment with the aperture. Another drawback of said design is that pressure containment and seal integrity are limited by the difficulty of molding a sufficiently thick membrane support plate and the incomplete support provided to the sealing area of the membrane due to permeate outlet passages that directly cross the seal area. The problems caused by frictional forces on the membrane and incomplete seal support are further exacerbated when the membrane is not first sealed to the concentration chamber, but sealing and assembly rather are effected in a single operation by compression during application of the perimeter of the membrane to the aperture of the concentration chamber.
UK Application No. 9819686.8 discloses a so-called tangential flow filtration device. The drawback of this device is the need to machine its component parts due to the difficulty of molding them sufficiently thick to contain high pressures. In addition, relatively expensive bolting mechanisms are required to hold the assembled device together sufficiently tightly to resist high operating pressures.
One object of the present invention is to provide a device of the type mentioned above which is simple to manufacture while providing increased overall reliability.
A further object is to provide a device for which it is possible to choose materials for the retentate and permeate compartments which do not require heat or ultrasonic seal compatibility with each other nor with the membrane used.
A further object is to provide a device which has a supported seal around the entire periphery of the membrane.
A further object of the invention is to provide a device which is possible to reopen and reclose, after processing in order to inspect and/or replace the membrane without damaging the retentate or permeate compartments or the membrane.
A still further object is to provide a method according to which the membrane will be sealed to the filtration device during assembly in a single operation.
The foregoing objects, uses and advantages of this invention will become apparent from the following description.